Medical cannabis for children: Evidence and recommendations.

Interest in using cannabis products for a medical purpose in children under the age of 18 years is increasing. There are many medical cannabis products available that can include cannabidiol (CBD) or delta-9-tetrahydrocannabinol (THC), or both. Despite many therapeutic claims, there are few rigorous studies to inform the dosing, safety, and efficacy of medical cannabis in paediatric clinical practice. This statement reviews the current evidence and provides recommendations for using medical cannabis in children. Longer-term (2-year) reports support the sustained tolerability and efficacy of cannabidiol therapy for patients with Lennox-Gastaut and Dravet syndromes. CBD-enriched cannabis extracts containing small amounts of THC have been evaluated in a small number of paediatric patients, and further research is needed to inform clinical practice guidelines. Given the widespread use of medical cannabis in Canada, paediatricians should be prepared to engage in open, ongoing discussions with families about its potential benefits and risks, and develop individualized plans that monitor efficacy, reduce harms, and mitigate drug-drug interactions.

Les données probantes et les recommandations sur le cannabis à des fins médicales chez les enfants.

L'intérêt envers l'utilisation des produits du cannabis à des fins médicales chez les enfants de moins de 18 ans augmente. De nombreux produits du cannabis à des fins médicales contiennent du cannabidiol, du delta-9-tétrahydrocannabinol ou ces deux produits. Malgré les nombreuses prétentions thérapeutiques, peu d'études rigoureuses guident la posologie, l'innocuité et l'efficacité du cannabis à des fins médicales en pédiatrie clinique. Le présent document de principes passe en revue les données probantes à jour et expose les recommandations sur l'utilisation du cannabis à des fins médicales chez les enfants. Les rapports à plus long terme (deux ans) souscrivent à la tolérabilité et à l'efficacité soutenues d'un traitement au cannabidiol chez les patients ayant le syndrome de Lennox-Gastaut ou le syndrome de Dravet. Les extraits de cannabis enrichis de cannabidiol qui renferment de petites quantités de delta-9-tétrahydrocannabinol ont été évalués auprès d'un petit nombre de patients d'âge pédiatrique, et d'autres recherches devront être réalisées pour éclairer les guides de pratique clinique. Étant donné l'utilisation répandue du cannabis à des fins médicales au Canada, les pédiatres devraient être prêts à participer à des échanges ouverts et continus avec les familles au sujet de ses avantages potentiels et de ses risques, ainsi qu'à préparer des plans individuels en vue d'en surveiller l'efficacité, de réduire les méfaits et de limiter les interactions médicamenteuses.

Is EGD Needed in all Patients after Suicidal or Exploratory Caustic Ingestions?

BACKGROUND: Caustic ingestions are relatively uncommon, but remain a significant source of morbidity. Patients with caustic injury often undergo an urgent EGD, although it is not clear if an EGD is routinely needed in an asymptomatic patient. The study has two primary objectives; 1) to determine the utility of routine EGD in asymptomatic suicidal caustic ingestions; 2) to determine if asymptomatic unintentional acidic ingestions can be managed with observation alone, similar to basic ingestions. METHODS: This retrospective study, which took place at 14 hospitals in three countries evaluated all patients who presented with a caustic ingestion between 2014-2020. The presence of symptoms and esophageal injury, demographic information, pH of ingested substance, reason for the ingestion, and outcome were recorded. RESULTS: 409 patients were identified; 203 (46.9%) were male. The median (IQR) age was 18 (4-31) years; overall range 10 months to 78 years. Suicidal ingestions accounted for 155 (37.9%) of cases. Dysphagia or dysphonia were more likely in those with significant esophageal injury compared to those without (59.3% vs. 12.6% respectively; OR 10.1; 95% CI 4.43-23.1). Among 27 patients with significant esophageal injury, 48% were found in suicidal patients, compared with 51.9% in non-suicidal patients (p = NS). On multivariate regression, there was no difference in the rate of significant esophageal injury among suicidal vs. non suicidal patients (aOR 1.55; p = 0.45, 95% CI 0.45-5.33). Most ingestions involved basic substances (332/409; 81.2%). Unknown or mixed ingestions accounted for 25 (6.11%) of the ingestions. Significant esophageal burns were found in 6/52 (11.5%) of acid ingestions, compared with 21/332 (6.3%) of basic ingestions. Of the 42 cases of acidic ingestions without dysphagia or odynophagia, 2 (4.8%; 0.58-16.1%) had significant esophageal burns, compared with 9 (3.2%; 95% CI 1.4-5.9%) of the 284 basic ingestions; p = 0.64). On multivariate logistic regression, patients with acidic ingestions were not more likely to experience a significant burn (aOR 1.7; p = 0.11, 95% CI 0.9-3.1) compared to those with basic ingestions. No patient with significant esophageal burns was asymptomatic. CONCLUSION: In this study, there was no statistical differences in the rates of significant burns between acidic and basic caustic ingestions. There were no significant esophageal injuries noted among asymptomatic patients.

Household Transmission Dynamics of Asymptomatic SARS-CoV-2-Infected Children: A Multinational, Controlled Case-Ascertained Prospective Study.

BACKGROUND: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described. METHODS: In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls. After 14 days' follow-up we assessed the clinical (ie, symptomatic) and combined (ie, test-positive, or symptomatic) secondary attack rates (SARs) among household contacts. Additionally, post-COVID-19 condition (PCC) was assessed in SARS-CoV-2-positive participating children after 90 days' follow-up. RESULTS: A total of 111 test-positive and 256 SARS-CoV-2 test-negative asymptomatic children were enrolled between January 2021 and April 2022. After 14 days, excluding households with co-primary cases, the clinical SAR among household contacts of SARS-CoV-2-positive and -negative index children was 10.6% (19/179; 95% CI: 6.5%-16.1%) and 2.0% (13/663; 95% CI: 1.0%-3.3%), respectively (relative risk = 5.4; 95% CI: 2.7-10.7). In households with a SARS-CoV-2-positive index child, age <5 years, being pre-symptomatic (ie, developed symptoms after test), and testing positive during Omicron and Delta circulation periods (vs earlier) were associated with increased clinical and combined SARs among household contacts. Among 77 asymptomatic SARS-CoV-2-infected children with 90-day follow-up, 6 (7.8%; 95% CI: 2.9%-16.2%) reported PCC. CONCLUSIONS: Asymptomatic SARS-CoV-2-infected children, especially those <5 years, are important contributors to household transmission, with 1 in 10 exposed household contacts developing symptomatic illness within 14 days. Asymptomatic SARS-CoV-2-infected children may develop PCC.

Exploring the Possible Role of Cannabinoids in Managing Post-Cardiac Surgery Complications: A Narrative Review of Preclinical Evidence and a Call for Future Research Directions.

Open-heart surgery with cardiopulmonary bypass (CPB) often leads to complications including pain, systemic inflammation, and organ damage. Traditionally managed with opioids, these pain relief methods bring potential long-term risks, prompting the exploration of alternative treatments. The legalization of cannabis in various regions has reignited interest in cannabinoids, such as CBD, known for their anti-inflammatory, analgesic, and neuroprotective properties. Historical and ongoing research acknowledges the endocannabinoid system's crucial role in managing physiological processes, suggesting cannabinoids could offer therapeutic benefits in post-surgical recovery. Specifically, CBD has shown promise in managing pain, moderating immune responses, and mitigating ischemia/reperfusion injury, underscoring its potential in postoperative care. However, the translation of these findings into clinical practice faces challenges, highlighting the need for extensive research to establish effective, safe cannabinoid-based therapies for patients undergoing open-heart surgery. This narrative review advocates for a balanced approach, considering both the therapeutic potential of cannabinoids and the complexities of their integration into clinical settings.

Removing barriers to accessing medical cannabis for paediatric patients.

Medical cannabis (MC) may offer therapeutic benefits for children with complex neurological conditions and chronic diseases. In Canada, parents, and caregivers frequently report encountering barriers when accessing MC for their children. These include negative preconceived notions about risks and benefits, challenges connecting with a knowledgeable healthcare provider (HCP), the high cost of MC products, and navigating MC product shortages. In this manuscript, we explore several of these barriers and provide recommendations to decision-makers to enable a family-centered and evidence-based approach to MC medicine and research for children.

Unintentional pediatric poisonings before and during the COVID-19 pandemic: A population-based study.

OBJECTIVES: The impact of coronavirus disease 2019 (COVID-19) on unintentional pediatric poisonings is unclear. We examined changes in emergency department (ED) visits and hospitalizations for poisonings before and during the COVID-19 pandemic. We compared changes in cannabis vs non-cannabis poisoning events given the recent legalization of cannabis in October 2018 and cannabis edibles in January 2020. STUDY DESIGN: Interrupted time-series (ITS) analyses of changes in population-level ED visits and hospitalizations for poisonings in children aged 0-9 years in Ontario, Canada (annual population of 1.4 million children), over two time periods: pre-pandemic (January 2010-March 2020) and pandemic (April 2020-December 2021). RESULTS: Overall, there were 28,292 ED visits and 2641 hospitalizations for unintentional poisonings. During the pandemic, poisonings per 100,000 person-years decreased by 14.6% for ED visits (40.15 pre- vs. 34.29 during) and increased by 35.9% for hospitalizations (3.48 pre- vs. 4.73 during). ED visits dropped immediately (Incidence Rate Ratio [IRR], 0.76; 95% CI, 0.70-0.82) at the onset of the pandemic, followed by a gradual return to baseline (quarterly change, IRR 1.04, 95%CI 1.03-1.06), while hospitalizations had an immediate increase (IRR 1.34; 95% CI, 1.08-1.66) and no gradual change. The only increase in poisonings was for cannabis which had a 10.7-fold for ED visits (0.45 to 4.83 per 100,000 person-years) and a 12.1-fold increase for hospitalizations (0.16 to 1.91 per 100,000 person-years). Excluding cannabis, there was no overall increase in poisoning hospitalizations. CONCLUSIONS: The COVID-19 pandemic was not associated with increases in any type of unintentional pediatric poisonings, with the exception of cannabis poisonings. Increased cannabis poisonings may be explained by the legalization of non-medical cannabis edibles in Canada in January 2020.

Nasal Suctioning Therapy Among Infants With Bronchiolitis Discharged Home From the Emergency Department: A Randomized Clinical Trial.

Importance: Although nasal suctioning is the most frequently used supportive management for bronchiolitis, its benefit remains unknown. Objective: To evaluate the effectiveness of enhanced vs minimal nasal suctioning in treating infants with bronchiolitis after discharge from the emergency department (ED). Design, Setting, and Participants: This single-blind, parallel-group, randomized clinical trial was conducted from March 6, 2020, to December 15, 2022, at 4 tertiary-care Canadian pediatric EDs. Participants included otherwise healthy infants aged 1 to 11 months with a diagnosis of bronchiolitis who were discharged home from the ED. Interventions: Participants were randomized to minimal suctioning via bulb or enhanced suctioning via a battery-operated device before feeding for 72 hours. Main Outcomes and Measures: The primary outcome was additional resource use, a composite of unscheduled revisits for bronchiolitis or use of additional suctioning devices for feeding and/or breathing concerns. Secondary outcomes included health care utilization, feeding and sleeping adequacy, and satisfaction. Results: Of 884 screened patients, 352 were excluded for criteria, 79 declined participation, 81 were otherwise excluded, 372 were randomized (185 to the minimal suction group and 187 to the enhanced suction group), and 367 (median [IQR] age, 4 [2-6] months; 221 boys [60.2%]) completed the trial (184 in the minimal suction and 183 in the enhanced suction group). Additional resource use occurred for 68 of 184 minimal suction participants (37.0%) vs 48 of 183 enhanced suction participants (26.2%) (absolute risk difference, 0.11; 95% CI, 0.01 to 0.20; P = .03). Unscheduled revisits occurred for 47 of 184 minimal suction participants (25.5%) vs 40 of 183 enhanced suction participants (21.9%) (absolute risk difference, 0.04; 95% CI, -0.05 to 0.12; P = .46). A total of 33 of 184 parents in the minimal suction group (17.9%) used additional suctioning devices vs 11 of 183 parents in the enhanced suction group (6.0%) (absolute risk difference, 0.12; 95% CI, 0.05 to 0.19; P < .001). No significant between-group differences were observed for all bronchiolitis revisits (absolute risk difference, 0.07; 95% CI, -0.02 to 0.16; P = .15), ED revisits (absolute risk difference, 0.04; 95% CI, -0.03 to 0.12; P = .30), parental care satisfaction (absolute risk difference, -0.02; 95% CI, -0.10 to 0.06; P = .70), and changes from baseline to 72 hours in normal feeding (difference in differences, 0.03; 95% CI, -0.10 to 0.17; P = .62), normal sleeping (difference in differences, 0.05; 95% CI, -0.08 to 0.18; P = .47), or normal parental sleeping (difference in differences, 0.10; 95% CI, -0.02 to 0.23; P = .09). Parents in the minimal suction group were less satisfied with the assigned device (62 of 184 [33.7%]) than parents in the enhanced suction group (145 of 183 [79.2%]) (risk difference, 0.45; 95% CI, 0.36 to 0.54; P < .001). Conclusions and Relevance: Compared with minimal suctioning, enhanced suctioning after ED discharge with bronchiolitis did not alter the disease course because there were no group differences in revisits or feeding and sleeping adequacy. Minimal suctioning resulted in higher use of nonassigned suctioning devices and lower parental satisfaction with the assigned device. Trial Registration: ClinicalTrials.gov Identifier: NCT03361371.

Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children.

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 109/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 109/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.

Transition to Schizophrenia Spectrum Disorder Following Emergency Department Visits Due to Substance Use With and Without Psychosis.

Importance: Episodes of substance-induced psychosis are associated with increased risk of developing a schizophrenia spectrum disorder. However, there are limited data on the transition risk for substance use without psychosis. Objectives: To quantify the risk of transition to schizophrenia spectrum disorder following an incident emergency department (ED) visit for (1) substance-induced psychosis and (2) substance use without psychosis and to explore factors associated with transition. Design, Settings, and Participants: A population-based retrospective cohort study (January 2008 to March 2022) of all individuals, aged 14 to 65 years, in Ontario, Canada, with no history of a psychotic disorder. Individuals with incident ED visits for substance use with and without psychosis were compared with members of the general population. Main Outcomes and Measures: Transition to schizophrenia spectrum disorder using a chart-validated algorithm. Associations between ED visits for substance use and subsequent transition were estimated using cause-specific hazard models. Results: The study included 9 844 497 individuals, aged 14 to 65 years (mean [SD] age, 40.2 [14.7] years; 50.2% female) without a history of psychosis. There were 407 737 individuals with an incident ED visit for substance use, of which 13 784 (3.4%) ED visits were for substance-induced psychosis. Individuals with substance-induced psychosis were at a 163-fold (age- and sex-adjusted hazard ratio [aHR], 163.2; 95% CI, 156.1-170.5) increased risk of transitioning, relative to the general population (3-year risk, 18.5% vs 0.1%). Individuals with an ED visit for substance use without psychosis had a lower relative risk of transitioning (aHR, 9.8; 95% CI, 9.5-10.2; 3-year risk, 1.4%), but incurred more than 3 times the absolute number of transitions (9969 vs 3029). Cannabis use had the highest transition risk among visits with psychosis (aHR, 241.6; 95% CI, 225.5-258.9) and the third-highest risk among visits without psychosis (aHR, 14.3; 95% CI, 13.5-15.2). Younger age and male sex were associated with a higher risk of transition, and the risk of male sex was greater in younger compared with older individuals, particularly for cannabis use. Conclusions and Relevance: The findings of this cohort study suggest that ED visits for substance use were associated with an increased risk of developing a schizophrenia spectrum disorder. Although substance-induced psychoses had a greater relative transition risk, substance use without psychosis was far more prevalent and resulted in a greater absolute number of transitions. Several factors were associated with higher transition risk, with implications for counseling and early intervention.

Lipid emulsion therapy during management of the critically-ill poisoned patient: a prospective cohort study.

BACKGROUND: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity. METHODS: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration. RESULTS: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis (P = 0.89) or polynomial model (P = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration. CONCLUSION: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

Severe outcomes following pediatric cannabis intoxication: a prospective cohort study of an international toxicology surveillance registry.

INTRODUCTION: An increasing number of jurisdictions have legalized recreational cannabis for adult use. The subsequent availability and marketing of recreational cannabis has led to a parallel increase in rates and severity of pediatric cannabis intoxications. We explored predictors of severe outcomes in pediatric patients who presented to the emergency department with cannabis intoxication. METHODS: In this prospective cohort study, we collected data on all pediatric patients (<18 years) who presented with cannabis intoxication from August 2017 through June 2020 to participating sites in the Toxicology Investigators Consortium. In cases that involved polysubstance exposure, patients were included if cannabis was a significant contributing agent. The primary outcome was a composite severe outcome endpoint, defined as an intensive care unit admission or in-hospital death. Covariates included relevant sociodemographic and exposure characteristics. RESULTS: One hundred and thirty-eight pediatric patients (54% males, median age 14.0 years, interquartile range 3.7-16.0) presented to a participating emergency department with cannabis intoxication. Fifty-two patients (38%) were admitted to an intensive care unit, including one patient who died. In the multivariable logistic regression analysis, polysubstance ingestion (adjusted odds ratio = 16.3; 95% confidence interval: 4.6-58.3; P < 0.001)) and cannabis edibles ingestion (adjusted odds ratio = 5.5; 95% confidence interval: 1.9-15.9; P = 0.001) were strong independent predictors of severe outcome. In an age-stratified regression analysis, in children older than >10 years, only polysubstance abuse remained an independent predictor for the severe outcome (adjusted odds ratio 37.1; 95% confidence interval: 6.2-221.2; P < 0.001). As all children 10 years and younger ingested edibles, a dedicated multivariable analysis could not be performed (unadjusted odds ratio 3.3; 95% confidence interval: 1.6-6.7). CONCLUSIONS: Severe outcomes occurred for different reasons and were largely associated with the patient's age. Young children, all of whom were exposed to edibles, were at higher risk of severe outcomes. Teenagers with severe outcomes were frequently involved in polysubstance exposure, while psychosocial factors may have played a role.

Significantly Longer Shedding of Norovirus Compared to Rotavirus and Adenovirus in Children with Acute Gastroenteritis.

Worldwide, acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children under 5 years of age. Viruses, including norovirus, rotavirus, and enteric adenovirus, are the leading causes of pediatric AGE. In this prospective cohort study, we investigated the viral load and duration of shedding of norovirus, rotavirus, and adenovirus in stool samples collected from 173 children (median age: 15 months) with AGE who presented to emergency departments (EDs) across Canada on Day 0 (day of enrollment), and 5 and 28 days after enrollment. Quantitative RT-qPCR was performed to assess the viral load. On Day 0, norovirus viral load was significantly lower compared to that of rotavirus and adenovirus (p < 0.001). However, on Days 5 and 28, the viral load of norovirus was higher than that of adenovirus and rotavirus (p < 0.05). On Day 28, norovirus was detected in 70% (35/50) of children who submitted stool specimens, while rotavirus and adenovirus were detected in 52.4% (11/24) and 13.6% (3/22) of children (p < 0.001), respectively. Overall, in stool samples of children with AGE who presented to EDs, rotavirus and adenovirus had higher viral loads at presentation compared to norovirus; however, norovirus was shed in stool for the longest duration.

Intravenous Magnesium: Prompt Use for Asthma in Children Treated in the Emergency Department (IMPACT-ED): Protocol for a Multicenter Pilot Randomized Controlled Trial.

BACKGROUND: Children managed for asthma in an emergency department (ED) may be less likely to be hospitalized if they receive intravenous magnesium sulfate (IVMg). Asthma guidelines recommend IVMg for severely sick children but note a lack of evidence to support this recommendation. All previous trials of IVMg in children with asthma have been too small to answer whether IVMg is effective and safe. A few major questions remain about IVMg. First, it has not been tested early in the course of ED treatment, when the impact on hospitalization would be greatest. Second, the clinical impact of hypotension, a known adverse effect of IVMg, has not been well characterized in previous research. Third, no trials have compared different IVMg doses or serial serum magnesium (total and ionized) concentrations to optimize dosing, so the most effective dose is unknown. A large, conclusive, randomized, placebo-controlled clinical trial of IVMg might be challenging due to the need to enroll and complete study procedures quickly, a lack of understanding of blood pressure changes after IVMg, and a lack of pharmacologic information to guide the optimal doses of IVMg to be tested. Therefore, a pilot study to inform the above gaps is warranted before conducting a definitive trial. OBJECTIVE: The objectives of this study are to (1) demonstrate the feasibility of enrolling children with severe acute asthma in the ED in a multicenter, randomized controlled trial of a placebo, low-dose IVMg, or high-dose IVMg; (2) demonstrate the feasibility of timely delivery of study medication, assessment of blood pressure, and evaluation of adverse events in a standardized protocol; and (3) externally validate a previously constructed pharmacokinetic model and develop a combined pharmacokinetic/pharmacodynamic model for IVMg using magnesium (total and ionized) serum concentrations and their correlation with measures of efficacy and safety. METHODS: This pilot trial tests procedures and gathers information to plan a definitive trial. The pilot trial will enroll as many as 90 children across 3 sites, randomize each child to 1 of 3 study arms, measure blood pressure frequently, and collect 3 blood samples from each participant with corresponding clinical asthma scores. RESULTS: The project was funded by the National Heart, Lung, and Blood Institute (1 R34HL152047-2) in March 2022. Enrollment began in September 2022, and 43 children have been enrolled as of April 2023. We will submit the results for publication in late 2023. CONCLUSIONS: The results of this study will guide the planning of a large, definitive, multicenter trial powered to evaluate if IVMg reduces hospitalization. Blood pressure measurements will inform a monitoring plan for the larger trial, and blood samples and asthma scores will be used to validate pharmacologic models to select the optimal dose of IVMg to be evaluated in the definitive trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05166811; https://clinicaltrials.gov/ct2/show/NCT05166811. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48302.

Intranasal ketamine for procedural sedation in children: An open-label multicenter clinical trial.

INTRODUCTION: There are limited options for pain and distress management in children undergoing minor procedures, without the burden of an intravenous line insertion. Prior to this study, we conducted a dose-escalation study and identified 6 mg/kg as a potentially optimal initial dose of intranasal ketamine. OBJECTIVE: To assess the efficacy and safety of intranasal ketamine at a dose of 6 mg/kg for procedural sedation to repair lacerations with sutures in children in the emergency department. METHODS: We conducted a single-arm, open-label multicenter clinical trial for intranasal ketamine for laceration repair with sutures in children aged 1 to 12 years. A convenience sample of 30 patients received 6 mg/kg of intranasal ketamine for their procedural sedation. The primary outcome was the proportion (95% CI) of patients who achieved an effective procedural sedation. RESULTS: We recruited 30 patients from April 2018 to December 2019 in two pediatric emergency departments in Canada. Lacerations repaired were mostly facial in 21(70%) patients and longer than 2 cm in 20 (67%) patients. Sedation was effective in 18/30 (60% [95% CI 45, 80]) children and was suboptimal in 5 (17%) patients but procedure was completed in them with minimal difficulties. Sedation was poor in the remaining 7 (23%) patients, with 3 (10%) of them required additional sedative agents. No serious adverse events were reported. CONCLUSIONS: Using a single dose of 6 mg/kg of intranasal Ketamine for laceration repair led to successful sedation in 60% of patients according to our a priori definition. An additional 17% of patients were considered suboptimal, but their procedure was still completed with minimal difficulty. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03053947).

Pediatric Hospitalizations for Unintentional Cannabis Poisonings and All-Cause Poisonings Associated With Edible Cannabis Product Legalization and Sales in Canada.

Importance: Canada legalized cannabis in October 2018 but initially prohibited the sale of edibles (eg, prepackaged candies). Starting in January 2020, some provinces permitted the sale of commercial cannabis edibles. The association of legalizing cannabis edibles with unintentional pediatric poisonings is uncertain. Objective: To evaluate changes in proportions of all-cause hospitalizations for poisoning due to cannabis in children during 3 legalization policy periods in Canada's 4 most populous provinces (including 3.4 million children aged 0-9 years). Design, Setting, and Participants: This repeated cross-sectional study included all hospitalizations in children aged 0 to 9 years in Ontario, Alberta, British Columbia, and Quebec between January 1, 2015, and September 30, 2021. Exposures: Prelegalization (January 2015 to September 2018); period 1, in which dried flower only was legalized in all provinces (October 2018 to December 2019); and period 2, in which edibles were legalized in 3 provinces (exposed provinces) and restricted in 1 province (control province) (January 2020 to September 2021). Main Outcomes and Measures: The primary outcome was the proportion of hospitalizations due to cannabis poisoning out of all-cause poisoning hospitalizations. Data analysis was performed using descriptive statistics and Poisson regression models. Results: During the 7-year study period, there were 581 pediatric hospitalizations for cannabis poisoning (313 [53.9%] boys; 268 [46.1%] girls; mean [SD] age, 3.6 [2.5] years) and 4406 hospitalizations for all-cause poisonings. Of all-cause poisoning hospitalizations, the rate per 1000 due to cannabis poisoning before legalization was 57.42 in the exposed provinces and 38.50 in the control province. During period 1, the rate per 1000 poisoning hospitalizations increased to 149.71 in the exposed provinces (incidence rate ratio [IRR], 2.55; 95% CI, 1.88-3.46) and to 117.52 in the control province (IRR, 3.05; 95% CI, 1.82-5.11). During period 2, the rate per 1000 poisoning hospitalizations due to cannabis more than doubled to 318.04 in the exposed provinces (IRR, 2.16; 95% CI, 1.68-2.80) but remained similar at 137.93 in the control province (IRR, 1.18; 95% CI, 0.71-1.97). Conclusions and Relevance: This cross-sectional study found that following cannabis legalization, provinces that permitted edible cannabis sales experienced much larger increases in hospitalizations for unintentional pediatric poisonings than the province that prohibited cannabis edibles. In provinces with legal edibles, approximately one-third of pediatric hospitalizations for poisonings were due to cannabis. These findings suggest that restricting the sale of legal commercial edibles may be key to preventing pediatric poisonings after recreational cannabis legalization.